IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system.

Immune cells function in an interacting hierarchy that coordinates the activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology.

Caspase-8 isoform 6 promotes death effector filament formation independent of microtubules.

Caspase-8 can trigger cell death following prodomain-mediated recruitment to the 'death-inducing signaling complex.' The prodomain consists of two death effector domain (DED) motifs that undergo homotypic interactions within the cell. Aside from mediating recruitment of procaspase-8, the prodomains have also been implicated in regulating cell survival, proliferation, death, senescence, differentiation, and substrate attachment. Here, we perform the initial characterization of a novel isoform of caspase-8, designated caspase-8 isoform 6 (Casp-8.6), which encodes both prodomain DEDs followed by a unique C-terminal tail. Casp-8.6 is detected in cells of the hematopoietic compartment as well as several other tissues. When Casp-8.6 expression is reconstituted in caspase-8-deficient cells, Casp-8.6 does not significantly impact cellular proliferation, contrasting with our previous results using a domain-defined 'DED-only' construct that lacks the C-terminal tail. Like the DED-only construct, Casp-8.6 also robustly forms 'death effector' filaments, but in contrast to the DED construct, it does not exhibit a dependence upon intact microtubules to scaffold filament formation. Both types of death effector filaments promote apoptosis when expressed in the presence of full length caspase-8 (isoform 1). Together, the results implicate Casp-8.6 as a new physiological modulator of apoptosis.

Assessing student understanding of host pathogen interactions using a concept inventory.

As a group of faculty with expertise and research programs in the area of host-pathogen interactions (HPI), we are concentrating on students' learning of HPI concepts. As such we developed a concept inventory to measure level of understanding relative to HPI after the completion of a set of microbiology courses (presently eight courses). Concept inventories have been useful tools for assessing student learning, and our interest was to develop such a tool to measure student learning progression in our microbiology courses. Our teaching goal was to create bridges between our courses which would eliminate excessive overlap in our offerings and support a model where concepts and ideas introduced in one course would become the foundation for concept development in successive courses. We developed our HPI concept inventory in several phases. The final product was an 18-question, multiple-choice concept inventory. In fall 2006 and spring 2007 we administered the 18-question concept inventory in six of our courses. We collected pre- and postcourse surveys from 477 students. We found that students taking pretests in the advanced courses retained the level of understanding gained in the general microbiology prerequisite course. Also, in two of our courses there was significant improvement on the scores from pretest to posttest. As we move forward, we will concentrate on exploring the range of HPI concepts addressed in each course and determine and/or create effective methods for meaningful student learning of HPI aspects of microbiology.